We hypothesize that cancer cells enter the blood of most patients at a very early stage in tumor development. We have developed a highly sensitive assay for detecting circulating epithelial cells in the blood. The method has been applied to detect the presence of circulating carcinoma cells in the blood of patients with breast cancer as well as healthy individuals with no known cancerous disease. The objectivity and reproducibility of the study has been assured by performing the study in a blinded fashion. The majority of patients with various stages of breast cancer had circulating carcinoma cells in numbers above the cut-off value established based on the results obtained in the control group. In this proposal, our studies will focus on breast cancer. However, the assay will detect adenocarcinoma cells from primary tumors in other organs as well. The major benefit would be that treatment of early-stage tumors translates into a greater survival. Other important benefits result from the use of the method to monitor the efficiency of various therapy regimens and predict a metastatic evolution of the disease. Having a very accurate prognostic indicator also allows the physician to provide the breast cancer patient with reliable information regarding his or her future survival and possible outcome. In addition, it will allow patients to make rational decision concerning the participation in various clinical trials and treatment regimens. In this project, we will focus on the following primary objectives: 1) Optimize the assay to enumerate and characterize the circulating tumor cells that are in the blood and/or bone marrow of patients with breast cancer or other carcinomas; 2)Determine the prognostic value of the assay; 3) Monitor the efficiency of certain regimens of adjuvant therapy for their ability to remove circulating carcinoma cells.